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南非艾滋病毒精英控制者的先天性免疫功能障碍和持续激活
Asisipo Mohamed1,2, Yenzekile Zungu1,2, Sharon Shalekoff1,2
1School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Frontiers in immunology
|September 12, 2025
概括
艾滋病毒的精英控制者保持病毒控制,但表现出受损的先天免疫反应,类似于其他艾滋病毒感染者. 这表明需要持续监测和干预来管理慢性炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 传染性疾病 传染性疾病
背景情况:
- 精英控制器 (PWH_EC) 在没有治疗的情况下自发控制HIV-1,但面临非艾滋病并发症.
- 与适应性免疫相比,对控制HIV-1的先天免疫反应的研究不足.
- 抗原呈现细胞 (APC) 在先天免疫和HIV-1病原发生过程中起着至关重要的作用.
研究的目的:
- 通过评估南非成年艾滋病毒感染者的APC表型和功能来评估先天免疫反应的质量.
- 为了比较艾滋病毒精英控制者,艾滋病毒进展者和未感染艾滋病毒的个体之间的先天免疫特征.
- 在不同艾滋病毒感染群体中识别免疫激活和炎症的潜在生物标志物.
主要方法:
- 对单细胞子集,T细胞和单细胞激活以及单细胞和树突细胞 (mDC,pDC) 中的细胞因子 (TNF-α,IFN-α,IL-1β) 生产的分析.
- 使用托尔类受体 (TLR) 配体 (LPS,CL097,CpG-ODN2216) 刺激细胞.
- 使用ELISA测量可溶性CD14 (sCD14) 和D-二元体等离子体生物标志物.
主要成果:
- 与未感染艾滋病毒的对照人群相比,在PWH_EC中减少了单细胞上的CD86表达和较低的经典单细胞频率.
- 在PWH_EC后刺激中,单细胞和mDCs减少TNF-α和IL-1β的产生.
- 在PWH_EC中增加的sCD14水平表明持续的免疫激活,在PWH_PROG中增加的D-二次体表明更高的炎症.
结论:
- PWH_EC表现出先天性免疫特征,其特征是单细胞激活减少,较少的经典单细胞,以及受损的促炎性细胞因子生产.
- 尽管有病毒控制,但PWH_EC表现出持续免疫激活和与不良结果相关的生物标志物升高的迹象.
- 这些发现强调了持续监测和治疗策略的必要性,以解决PWH_EC的慢性炎症.
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